Studies On Correlation Between Genetic Polymorphisms In Matrix Metalloproteinase Genes And The Risk Of Lung Cancer

Lung cancer is currently one of the most common malignant tumors in the world,with an increasing trend of morbidity and mortality.The major causes of lung cancer are inhaled carcinogens,such as tobacco and environmental pollution.Nevertheless,a growing number of researches have suggested that the incidence of lung cancer is closely related to genetic factors.Single nucleotide polymorphism(SNP)is the most common genetic variation in the human genome.Matrix metalloproteinases(MMPs),a family of Zn2+ dependent endopeptidases,play a key role in extracellular matrix(ECM)remodeling,especially in elastin and collagen turnover.MMP gene expression is regulated primarily at the transcriptional level,which is associated with tumor spread and patient prognosis.This study was aimed to analyse the relation between MMP9,MMP13 and MMP7 gene polymorphisms and the the susceptibility to lung cancer,either independently or joint,in Hunan.The main research contents were as follows:(1)This case-control study included 182 lung cancer patients and169 healthy controls.The basic data including age,gender and smoking status,and paramenters of clinical pathology.Genomic DNA was extracted by using DNA extraction kit.SNP of MMP9 was genotyped by polymerase chain reaction-restrictive fragment length polymorphism(PCR-RFLP)analysis and direct DNA sequencing,and Statistical analysis was performed using SPSS 19.0 software package.These findings suggested that smoking was a risk factor to lung cancer(P=0.001,χ2=17.33).Compared with the CT genotype,MMP9-1562 CC genotype might be a marker of increased genotype susceptibility to lung cancer among South-Central Chinese population(OR=2.39,95 % CI =1.45-3.92).However,the MMP9 was not associated with the clinical pathology parameters of lung cancer patients.(2)In the same method,the study included 182 lung cancer cases and 215 healthy controls.Association between the gene polymorphism-77A/G of MMP13 and lung cancer risk was to investigated.It showed that Smoking may increase the risk of developing lung cancer(P=0.00,χ2=27.13).Compared with the GG genotype,MMP13 AA genotype might be a marker of decreased susceptibility to lung cancer(OR=0.53,95 %CI=0.29-0.98).The MMP13 was not associated with the clinical pathology parameters of lung cancer patients.In additional,interaction between the MMP9 and MMP13 polymorphisms increased the incidence and development of lung cancer(OR=4.39,95 % CI = 2.08-9.26).(3)To examine associations between the gene polymorphism-181A/G of MMP7 and lung cancer risk,the third part of this research included 260 lung cancer cases and 219 healthy controls.It found that smoking was a high risk factor for lung cancer(χ2=26.51).Compared with the AA genotype,MMP7 AG genotype was significantly increased the risk of lung cancer(OR=1.75,95 % CI=1.15-2.69).Furthermore,this study also found that the MMP7 genotype was not associated with the clinical pathology parameters of lung cancer patients.